Further Improvement of Bacillus subtilis cell factory Producing scyllo-Inositol, a Promising Therapeutic Agent for Alzheimer's Disease

scyllo-Inositol (SI) is one of the inositol stereoisomers, rare in the nature, and expected as a promising disease-modifying therapeutic agent for Alzheimer's disease. On the other hand, myo-inositol (MI) is another inositol stereoisomer most abundant in nature and thus supplied cheap from agricultural wastes including rice bran.

By using Bacillus subtilis strains with genetic modifications in inositol metabolism, we have developed the bioconversion processes from MI into SI. Previously, in a modified strain inactive in inositol catabolism, the constitutive and simultaneous overexpression of IolG and IolW, which are the two inositol dehydrogenases responsible for the conversion, enabled us to demonstrate an efficient conversion with a rate up to 10 g/ L/ 48 h.

In order to devise further elevation in the conversion efficiency, we attempted to improve the substrate uptake by overexpressing iolT for the major MI transporter. In addition, E. coli pntAB encoding the membrane-bound transhydrogenase was introduced aiming at enhanced supply of NADPH required for the rate-limiting IolW reaction. These two additional modifications successfully elevated the conversion efficiency with an improved rate up to 18 g/ L/ 48h.